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Neurologic Illness Associated with Occupational Exposure
to the Solvent 1-Bromopropane --- New Jersey and Pennsylvania, 2007--2008

1-Bromopropane (1-BP) (n-propyl bromide) is a solvent increasingly used as a substitute for ozone-depleting
chloro-fluorocarbons and similar regulated compounds. 1-BP is used in vapor and immersion degreasing operations and
other manufacturing processes, and as a solvent in industries using aerosol-applied adhesives. In some states, 1-BP is used as
a solvent in dry cleaning because of restrictions on use of perchloroethylene (tetrachloroethylene), a possible human
carcinogen (1). Published studies of workers exposed to 1-BP have raised concerns about occupational health risks associated
with exposure (2--5). This report describes two cases involving workers exposed to 1-BP and diagnosed with clinical
manifestations of neurotoxicity. The cases, when coupled with previously reported studies of workers exposed to 1-BP, illustrate
potential health risks of 1-BP exposure. Clinicians and public health professionals should be alert to potential health effects
among workers exposed to 1-BP, particularly in dry cleaning and other workplaces where 1-BP use might be increasing, and
effective control methods to limit exposure to 1-BP should be implemented at worksites.

Both cases involved neurotoxic effects that likely resulted from occupational exposure to 1-BP in the electronics and
dry cleaning industries. The cases were reported to regional poison control centers in Pennsylvania (2007) and New Jersey
(2008) by attending physicians who treated the affected workers. The cases were investigated by federal and state health agencies,
and more in-depth investigations of the New Jersey case currently are being conducted by the New Jersey Department of
Health and Senior Services and CDC.

Case 1. In 2007, a male aged 50 years visited an emergency department in Pennsylvania with a history of
confusion, dysarthria, dizziness, paresthesias, and ataxia for 24--48 hours. The patient had worked for 8 years at an electronics plant
in Pennsylvania, where for 3 years 1-BP had been used to clean circuit boards by vapor and immersion degreasing. His duties
at the plant included mechanically submerging and spraying circuit boards with 1-BP, and maintenance (draining, cleaning,
and charging) of the bath tank. The patient typically did not use personal protective equipment (PPE), and ventilation
was reported by the patient to be poor within the process room. Neurologic examination revealed that the patient was alert
but had slowed mental activity and mild confusion. His cranial nerve function and motor strength were intact, but his gait
was
wide based and ataxic, and a Romberg's test was positive. Serum laboratory results were notable for an anion gap of -31
mmol/L (normal range: 5--17 mmol/L) and a chloride concentration of 146 mmol/L (normal range: 101--111 mmol/L). The
patient was hospitalized. Mild sensory peripheral neuropathy was detected by electromyogram in his upper and lower extremities.

One week after the patient went to the emergency department, the Occupational Safety and Health
Administration (OSHA) evaluated his workplace and found a 1-BP concentration of 178 ppm by short-term area air sampling. Two
weeks after his initial visit to the emergency department, the patient's serum bromide concentration was 48 mg/dL (normal range:
0--10 mg/dL). His peripheral neuropathy and ataxia persisted 1 year after the initial visit. The patient also reported
having trouble maintaining mental focus and stopped working at the electronic plant because of continuing medical problems.

Case 2. A previously healthy male aged 43 years visited his primary-care physician in New Jersey in February 2008 with
a history of headache, nausea, dizziness, and malaise, which began after he had begun using 1-BP in his dry cleaning facility.
Six weeks earlier, the patient had switched from using perchloroethylene to DrySolv (Enviro Tech International, Melrose
Park, Illinois) (>95% by weight 1-BP) as the solvent in his dry cleaning machine
(7). The patient also used DrySolv as a cleaner
to prepare the dry cleaning machine for use. In early February 2008, he manually charged the machine using 50--60 gallons
of the solvent and did not use PPE. The patient then began using DrySolv in the daily operation of the dry cleaning
machine. During the next 2 days, he reported unusual fatigue and headaches and developed arthralgias, visual disturbances
(difficulty focusing), paresthesias, and muscular twitching.

The patient was referred by his personal physician to an emergency department, where physical examination and
computed tomography of his head were normal, except for a slight tremor in his upper extremities. Tests of the patient's serum
revealed an anion gap and chloride concentration within normal ranges. A site visit to the dry cleaning facility in April 2008 by
the New Jersey Department of Health and Senior Services revealed background and high peak concentrations (75 to 250
times background levels) of 1-BP during the handling of clothes. The patient continued to use 1-BP in the dry cleaning
machine but adjusted temperature settings on the machine to account for the physical properties of 1-BP, improved his use
of ventilation, and began using PPE.

Editorial Note:

1-BP has received increased global attention
since the 1990s as a potential alternative for
ozone-depleting chlorofluorocarbons and similar regulated compounds. Since its introduction within the United States, 1-BP has been applied as
a solvent in many industrial processes, including vapor degreasing, foam cushion manufacturing, and dry cleaning. The incidence of
1-BP toxicity is unknown, and the signs and symptoms are not described fully. In this report, case 1 demonstrated severe
neurologic illness in a worker in the electronics industry using 1-BP as a cleaning solvent. The elevated serum bromide concentration
and negative anion gap in a worker with neurologic abnormalities exposed to 1-BP provides strong evidence of occupational
1-BP toxicity. Although bromide levels were not measured in case 2, the
patient's clinical presentation and course, and his exposure to
1-BP, strongly favor the conclusion that his illness was caused by 1-BP. However, the exact etiology of the neurologic illnesses of the
two workers remains unclear and nonwork-related factors potentially contributing to the illnesses are not fully characterized.
Additionally, personal exposure information was not available for these workers to help establish their workplace exposures to 1-BP or to
other potential workplace hazards.

CDC does not have a recommended exposure limit for 1-BP, nor does OSHA have a permissible exposure limit. Manufacturers
of 1-BP and professional organizations, such as the American Conference of Governmental Industrial Hygienists, have
recommended occupational exposure limits ranging from 10 ppm to 100 ppm as an 8-hour time-weighted average
(6). On the basis of limited exposure and human health effects data, the National Toxicology Program concluded that exposure to 1-BP is toxic to
the developmental and reproductive health of animals
(8). Animal toxicity studies with 1-BP and human case reports of
occupational exposures to 1-BP have raised concerns that exposure to 1-BP might cause reproductive and neurologic effects
(2--6). Workers exposed to 1-BP vapors from spray adhesives at two seat-cushion--manufacturing facilities were found to have severe
neurologic illnesses (4,5). CDC evaluated workers at one of those facilities and found nonspecific acute effects (e.g., headache and feeling
drunk) possibly associated with central nervous system responses to 1-BP exposure
(2).

In accordance with its Significant New Alternatives Program, the Environmental Protection Agency (EPA) has
reviewed available scientific literature on 1-BP and promulgated a final rule to accept 1-BP as an alternative for ozone-depleting
solvents
in the solvent cleaning sector.* EPA also published a proposed rule not to accept 1-BP for use as an aerosol solvent vehicle
for adhesives because of higher exposures and the potential for adverse health effects to workers in these
settings. These new rules do not apply to dry cleaning.

Case 2 likely represents a sentinel case of neurologic toxicity in the dry cleaning industry, and additional cases could occur as
dry cleaners switch from perchloroethylene use to 1-BP. The U.S. dry cleaning and laundry industry employs an estimated
110,000 persons at approximately 30,000 establishments and is one of the largest industry sectors characterized by small businesses with
fewer than 10 employees. In recent years, an estimated 85%--90% of the dry cleaning industry has used perchloroethylene as a solvent.
In response to environmental and health concerns, certain states, including California and New Jersey
(9,10), have passed or proposed legislation to eliminate use of perchloroethylene as the primary solvent in the dry cleaning industry. To use 1-BP as an
alternative solvent, dry cleaning businesses must modify existing equipment to adjust heating/drying cycles, upgrade solvent vapor
control systems, replace natural rubber seals, and provide adequate exhaust ventilation. Manufacturer literature on the use of
DrySolv recommends wearing a full-facepiece organic vapor respirator if ventilation is inadequate, and chemical-resistant gloves for
skin protection (7). Previous CDC research and communication efforts have emphasized application of a hierarchy of controls
(e.g., engineering controls and work practices) for reducing worker exposures to
perchloroethylene.§ Similar controls should be used
within the dry cleaning industry to limit worker exposure to 1-BP.

Clinicians and public health officials should be alert to potential adverse health effects from exposures to 1-BP in
industries where such use might increase, such as the dry cleaning industry, and in workplaces where 1-BP use might be
more established. A thorough occupational history always should be part of the clinical evaluation of persons who have
unexplained or onset of nonspecific neurologic symptoms. Exposure to electronics cleaning solvents or dry cleaning solvents should
prompt a more through inquiry concerning exposure to 1-BP. In the evaluation of a worker with occupational exposure to 1-BP
and neurologic abnormalities, diagnosis of 1-BP poisoning is suggested by an elevated urinary or serum bromide
concentration and a negative serum anion gap. Findings of potential 1-BP poisoning in a potentially exposed worker should prompt
removal of the worker from the exposure while an evaluation of workplace exposures is conducted by a qualified professional.

Acknowledgment

The findings in this report are based, in part, on contributions by JB Nemhauser, MD, National Center for Environmental
Health, CDC.

National Toxicology Program-Center for the Evaluation of Risks to Human Reproduction. NTP-CERHR expert panel report on the
reproductive and developmental toxicity of 1-bromopropane. Reproduc Toxicol 2004;18:157--88.

New Jersey Department of Environmental Protection. Control and prohibition of air pollution by toxic substances. Trenton, NJ: New
Jersey Department of Environmental Protection; 2007. Available at
http://www.nj.gov/dep/rules/proposals/121707b.pdf.

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